DLG5

Chr 10AR

discs large MAGUK scaffold protein 5

Also known as: LP-DLG, P-DLG5, PDLG, YUVOB

NCBI Gene: 9231ENSG00000151208UniProt: Q8TDM6OMIM: 604090

This gene encodes a scaffolding protein that regulates the Hippo signaling pathway, controls cell proliferation and epithelial polarity, and plays important roles in dendritic spine formation and synaptogenesis in cortical neurons. Mutations cause Yuksel-Vogel-Bauser syndrome, which follows autosomal recessive inheritance. The gene is highly constrained against loss-of-function mutations in the general population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.261 OMIM phenotype
Clinical Summary— DLG5
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 30 VUS of 70 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.26LOEUF
pLI 0.999
Z-score 7.05
OE 0.17 (0.11–0.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.59Z-score
OE missense 0.79 (0.74–0.83)
919 obs / 1168.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.17 (0.11–0.26)
0≤0.351.4
Missense OE0.79 (0.74–0.83)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 14 / 83.5Missense obs/exp: 919 / 1168.0Syn Z: -0.80
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedDLG5-related developmental disorderLOFAD
limitedDLG5-related developmental disorderLOFAR
DN
0.3892th %ile
GOF
0.4184th %ile
LOF
0.74top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.26

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

70 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
VUS30
Likely Benign16
Benign16
Conflicting1
7
Pathogenic
30
VUS
16
Likely Benign
16
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
6
0
7
Likely Pathogenic
0
0
0
0
0
VUS
0
28
2
0
30
Likely Benign
0
5
4
7
16
Benign
0
4
3
9
16
Conflicting
—1
Total137151670

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DLG5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Genetic variants in Hippo pathway genes are associated with house dust mite-induced allergic rhinitis in a Chinese population
Chen M et al.·Clin Transl Allergy
2021
DLG5 variants are associated with multiple congenital anomalies including ciliopathy phenotypes
Marquez J et al.·J Med Genet
2021
Exploring a distinct FGFR2::DLG5 rearrangement in a low-grade neuroepithelial tumor: A case report and mini-review of protein fusions in brain tumors.
Loreto Palacio P et al.·J Neuropathol Exp Neurol
2024Review
LncRNA DLG5-AS1 facilitates breast cancer cell proliferation and invasion by promoting EZH2-mediated transcriptional silencing of SFRP1.
Cai Y et al.·Arch Biochem Biophys
2024
Decreased expression of Dlg5 is associated with a poor prognosis and epithelial-mesenchymal transition in squamous cell lung cancer
Che J et al.·J Thorac Dis
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The reduced DLG5 promotes doxorubicin resistance in breast cancer cells MCF-7 through regulating autophagy.
Che J et al.·Discov Oncol
2025Open Access
Quinacrine induces autophagy via the Dlg5/AKT pathway to inhibit osteosarcoma cell proliferation and suppresses migration and invasion through the Dlg5/Girdin pathway.
Li H et al.·Phytomedicine
2025
Identification of Oncogenic Alterations in 124 Cases of Pediatric Papillary Thyroid Carcinoma: BEND7::ALK, DLG5::RET, and CCDC30::ROS1 Fusions Induce MAPK Pathway Activation.
Liu Y et al.·Endocr Pathol
2025Cohort
Correlation analysis of DLG5 and PD-L1 expression in triple-negative breast cancer.
Che J et al.·BMC Cancer
2025Open Access
Dual effects of DLG5 (disks large homolog 5 gene) modulation on chemotherapy-induced thrombocytopenia and nausea/vomiting via the hippo signalling pathway.
Li M et al.·Br J Pharmacol
2025
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients